The Food Standards Agency is updating consumers on information relating to the emerging evidence on atypical scrapie in sheep and goats. This follows a statement issued last night by the Spongiform Encephalopathy Advisory Committee (SEAC), an independent expert scientific committee that advises Government.

SEAC has been considering the significance of atypical scrapie, a brain disease of the type known as transmissible spongiform encephalopathies (TSEs) that affects sheep and goats. The most well known TSE is one that affects cattle: BSE. Sheep are known to get another TSE known as classical scrapie. Unlike BSE, classical scrapie is not known to be linked to any human disease. To date, BSE has not been found in the current UK sheep flock, although surveillance is ongoing.In 2003 the FSA Board first discussed emerging evidence of the possible existence of atypical scrapie (then referred to as anomalous or unconfirmed scrapie) and acknowledged uncertainties about the significance of these findings. Since then, scientists in the UK and internationally, including SEAC members, have been working to better understand the significance of these findings. A record of the discussion is available at the link to the minutes of the meeting below.

A SEAC statement published following its meeting on 24 February looks at the potential impact of atypical scrapie on human and animal health. SEAC concluded that: 'atypical scrapie could reliably be distinguished both from classical scrapie and from experimental BSE in sheep'. The SEAC statement also concludes, 'there is no evidence to date that atypical scrapie can infect humans, although a theoretical risk cannot be excluded'.

The FSA Board will have an initial discussion of the significance of these findings at its open Board meeting on 9 March 2006. In the meantime, the Agency’s advice on the risk of eating sheep and goats remains unchanged. The FSA is not advising people to stop eating sheep or goat meat or products.

Dr Alison Gleadle, Head of the FSA’s TSE Division, said: 'The Food Standards Agency has always been open about the uncertainty surrounding the possible risk of BSE and other brain diseases in sheep. Emerging evidence and expert opinion is pointing to more uncertainty. Much more work is needed before we can form a clearer picture of what, if any, risk there might be to people. While FSA advice remains that we are not advising people to stop eating sheep and goats, this issue will be discussed thoroughly by our Board and kept under review as evidence emerges.'

The FSA Board will discuss atypical scrapie and the possible risk to public health at its open meeting in Glasgow on 9 March. At its following meeting in April, the Board will also look at possible options for further precautionary risk reduction measures.

Notes to editors 1. The Spongiform Encephalopathy Advisory Committee (SEAC) is appointed by Ministers and sponsored jointly by the Department for Environment, Food and Rural Affairs (DEFRA), the Department of Health and the Food Standards Agency (FSA). Its role is to provide independent expert scientific advice to the Government on spongiform encephalopathies such as BSE, CJD and scrapie. SEAC's remit is wide-ranging, and covers public health, food safety and animal health issues. For further information about SEAC please see the SEAC website available at the link below. 2. Due to controls to protect consumers from BSE, all parts most likely to carry BSE infectivity are removed from cattle and sheep before entering the food chain.

These parts are referred to as Specified Risk Material (SRM).

However, BSE-infected sheep are thought to have similar tissue distribution of infectivity to scrapie-infected sheep.

This means that the existing SRM controls would be insufficient to eliminate all the risk of exposure to BSE infectivity.

Nevertheless these SRM controls offer further protection to consumers should research reveal atypical scrapie poses a risk to human health.

In addition, SEAC refers to SRM controls in its statement, saying: 'The available evidence suggests that, unlike experimental BSE in sheep, atypical scrapie may be absent from the lympho reticular system. Thus, assuming SRM regulations remain in place, if atypical scrapie can be transmitted to human, it may pose a relatively lower health risk than BSE if it ever enters the sheep flock. However, one study using oral delivery to a VRQ sheep suggests that PrPres may be present in the LRS. It is urgent to clarify this issue.'

The Committee met on November 9, 2005, from 8:00am until 11:55am, Hershey Lodge and Convention Center, Hershey, Pennsylvania. The meeting was called to order by Dr. Jim Logan, chair, with vice chairman Dr. Joe D. Ross attending. There were 74 people in attendance.

The Scrapie Program Update was provided by Dr. Diane Sutton, National Scrapie Program Coordinator, United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS), Veterinary Services (VS). The complete text of the Status Report is included in these Proceedings.

Dr. Patricia Meinhardt, USDA-APHIS-VS-National Veterinary Services Laboratory (NVSL) gave the Update on Genotyping Labs and Discrepancies in Results. NVSL conducts investigations into discrepancies on genotype testing results associated with the Scrapie Eradication Program. It is the policy of the Program to conduct a second genotype test at a second laboratory on certain individual animals. Occasionally, there are discrepancies in those results. The NVSL conducts follow-up on these situations through additional testing on additional samples from the field and archive samples from the testing laboratories.

For the period of time from January 1, 2005, until October 15, 2005, there were 23 instances of discrepancies in results from 35 flocks. Of those 23 instances, 14 were caused by laboratory error (paperwork or sample mix-up), 3 results from field error, 5 were not completely resolved, and 1 originated from the use of a non-approved laboratory for the first test. As a result of inconsistencies, one laboratory’s certification was revoked by APHIS-VS.

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Infected and Source Flocks

As of September 30, 2005, there were 105 scrapie infected and source flocks. There were a total of 165** new infected and source flocks reported for FY 2005. The total infected and source flocks that have been released in FY 2005 was 128. The ratio of infected and source flocks cleaned up or placed on clean up plans vs. new infected and source flocks discovered in FY 2005 was 1.03 : 1*. In addition 622 scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2005, of which 130 were RSSS cases. Fifteen cases of scrapie in goats have been reported since 1990. The last goat case was reported in May 2005. Approximately 5,626 animals were indemnified comprised of 49% non-registered sheep, 45% registered sheep, 1.4% non-registered goats and 4.6% registered goats.

Regulatory Scrapie Slaughter Surveillance (RSSS)

RSSS was designed to utilize the findings of the Center for Epidemiology and Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at http://www.aphis.usda.gov/vs/ceah/cahm/Sheep/sheep.htm . RSSS started April 1,

2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks for clean-up. During FY 2005 collections increased by 32% overall and by 90% for black and mottled faced sheep improving overall program effectiveness and efficiency as demonstrated by the 26% decrease in percent positive black faced sheep compared to FY 2004. Samples have been collected from 62,864 sheep since April 1, 2003, of which results have been reported for 59,105 of which 209 were confirmed positive. During FY 2005, 33,137 samples were collected from 81 plants. There have been 130 NVSL confirmed positive cases (30 collected in FY 2004 and confirmed in FY 2005 and 100 collected and confirmed in FY 2005) in FY 2005. Face colors of these positives were 114 black, 14 mottled, 1 white and 1 unknown. The percent positive by face color is shown in the chart below.

As of October 04, 2005, 103,580 sheep and goat premises have been assigned identification numbers in the Scrapie National Generic Database. Official eartags have been issued to 73,807 of these premises.

*This number based on an adjusted 12 month interval to accommodate the 60 day period for setting up flock plans.

Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)

Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

12/10/76AGRICULTURAL RESEARCH COUNCILREPORT OF THE ADVISORY COMMITTE ON SCRAPIEOffice NoteCHAIRMAN: PROFESSOR PETER WILDY

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A The Present Position with respect to ScrapieA] The Problem

Scrapie is a natural disease of sheep and goats. It is a slowand inexorably progressive degenerative disorder of the nervous systemand it ia fatal. It is enzootic in the United Kingdom but not in allcountries.

The field problem has been reviewed by a MAFF working group(ARC 35/77). It is difficult to assess the incidence in Britain fora variety of reasons but the disease causes serious financial loss;it is estimated that it cost Swaledale breeders alone $l.7 M duringthe five years 1971-1975. A further inestimable loss arises from theclosure of certain export markets, in particular those of the UnitedStates, to British sheep.

It is clear that scrapie in sheep is important commercially andfor that reason alone effective measures to control it should bedevised as quickly as possible.

Recently the question has again been brought up as to whetherscrapie is transmissible to man. This has followed reports that thedisease has been transmitted to primates. One particularly luridspeculation (Gajdusek 1977) conjectures that the agents of scrapie,kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy ofmink are varieties of a single "virus". The U.S. Department ofAgriculture concluded that it could "no longer justify or permitscrapie-blood line and scrapie-exposed sheep and goats to be processedfor human or animal food at slaughter or rendering plants" (ARC 84/77)"The problem is emphasised by the finding that some strains of scrapieproduce lesions identical to the once which characterise the humandementias"

Whether true or not. the hypothesis that these agents might betransmissible to man raises two considerations. First, the safetyof laboratory personnel requires prompt attention. Second, actionsuch as the "scorched meat" policy of USDA makes the solution of theacrapie problem urgent if the sheep industry is not to suffergrievously.

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76/10.12/4.6

http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf

Like lambs to the slaughter31 March 2001Debora MacKenzieMagazine issue 2284What if you can catch old-fashioned CJD by eating meat from a sheep infectedwith scrapie?FOUR years ago, Terry Singeltary watched his mother die horribly from adegenerative brain disease. Doctors told him it was Alzheimer's, butSingeltary was suspicious. The diagnosis didn't fit her violent symptoms,and he demanded an autopsy. It showed she had died of sporadicCreutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming bychance into a killer. But Singeltary thinks otherwise. He is one of a numberof campaigners who say that some sCJD, like the variant CJD related to BSE,is caused by eating meat from infected animals. Their suspicions havefocused on sheep carrying scrapie, a BSE-like disease that is widespread inflocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weightto the campaigners' fears. To their complete surprise, the researchers foundthat one strain of scrapie causes the same brain damage in ...

Edited by D. Carleton Gajdusek, Centre National de la RechercheScientifique, Gif-sur-Yvette, France, and approved December 7, 2000(received for review October 16, 2000)

Abstract

There is substantial scientific evidence to support the notion that bovinespongiform encephalopathy (BSE) has contaminated human beings, causingvariant Creutzfeldt-Jakob disease (vCJD). This disease has raised concernsabout the possibility of an iatrogenic secondary transmission to humans,because the biological properties of the primate-adapted BSE agent areunknown. We show that (i) BSE can be transmitted from primate to primate byintravenous route in 25 months, and (ii) an iatrogenic transmission of vCJDto humans could be readily recognized pathologically, whether it occurs bythe central or peripheral route. Strain typing in mice demonstrates that theBSE agent adapts to macaques in the same way as it does to humans andconfirms that the BSE agent is responsible for vCJD not only in the UnitedKingdom but also in France. The agent responsible for French iatrogenicgrowth hormone-linked CJD taken as a control is very different from vCJD butis similar to that found in one case of sporadic CJD and one sheep scrapieisolate. These data will be key in identifying the origin of human cases ofprion disease, including accidental vCJD transmission, and could providebases for vCJD risk assessment.

Chronic wasting disease (CWD) is a transmissiblespongiform encephalopathy (TSE) of deer and elk,and little is known about its transmissibility to otherspecies. An important factor controllinginterspecies TSE susceptibility is prion protein (PrP)homology between the source and recipientspecies/genotypes. Furthermore, the efficiency with whichthe protease-resistant PrP (PrP-res) of onespecies induces the in vitro conversion of the normal PrP(PrP-sen) of another species to theprotease-resistant state correlates with the cross-speciestransmissibility of TSE agents. Here weshow that the CWD-associated PrP-res (PrPCWD) of cervidsreadily induces the conversion of recombinant cervid PrP-senmolecules to the protease-resistant state in accordancewith the known transmissibility of CWD between cervids. In contrast,PrPCWD-induced conversions of human and bovine PrP-sen weremuch less efficient, and conversion of ovine PrP-sen wasintermediate. These results demonstrate a barrier at themolecular level that should limit the susceptibility of these non-cervidspecies to CWD.

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Clearly, it is premature to draw firm conclusions about CWDpassing naturally into humans, cattle and sheep, but the presentresults suggest that CWD transmissions to humans would be aslimited by PrP incompatibility as transmissions of BSE or sheepscrapie to humans. Although there is no evidence that sheepscrapie has affected humans, it is likely that BSE has caused variantCJD in 74 people (definite and probable variant CJD cases todate according to the UK CJD Surveillance Unit). Given thepresumably large number of people exposed to BSE infectivity,the susceptibility of humans may still be very low compared withcattle, which would be consistent with the relatively inefficientconversion of human PrP-sen by PrPBSE. Nonetheless, sincehumans have apparently been infected by BSE, it would seem prudentto take reasonable measures to limit exposure of humans(as well as sheep and cattle) to CWD infectivity as has beenrecommended for other animal TSEs.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease ofsheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) thatwere exposed to the infectious agents only by their nonforced consumption ofknown infectious tissues. The asymptomatic incubation period in the onemonkey exposed to the virus of kuru was 36 months; that in the two monkeysexposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months,respectively; and that in the two monkeys exposed to the virus of scrapiewas 25 and 32 months, respectively. Careful physical examination of thebuccal cavities of all of the monkeys failed to reveal signs or orallesions. One additional monkey similarly exposed to kuru has remainedasymptomatic during the 39 months that it has been under observation.

Sir,- Creutzfeldt-Jakob disease (CJD) can be transmitted iatrogenically byhuman pituitary growth hormone, corneal transplants, and dura mater grafts(1). Possible accidental transmission has been reported in only fourpeople-a neurosurgeon (2), a pathologist (3), and two laboratory technicians(4,5) . We have encountered an unusually rapid case of CJD probably acquiredthrough handling of sheep and human dura mater.In May, 1992, a 55-year-old orthopaedic surgeon developed paraesthesia ofthe left arm. A few days later he had spatial disorientation, apraxia, andgait ataxia. In June he was admitted and a neurologist suspected CJD on thebasis of the clinical signs, typical electroencephalogram (EEG) pattern, andhistory. An EEG in June revealed a typical pattern of periodic biphasic andtriphasic sharp wave complexes. We saw the patient in July, 1992. He wasawake and oriented, with dyscalculia, dysgraphia, disturbed vision, apraxiamainly of the left side, rigidity of wrists, spasticity of all muscles,myoclonus of the left arm, increased tendon reflexes, ataxia of limbs andtrunk, and incoordination of left arm. Within 3 weeks he had impairedconsciousness and attention, mildly impaired memory, and threatening visualhallucinations with restless turning. He had periodic states with movementsof his head and eye-bulbs resembling tonic adversive seizures. During sleepthese motor disturbances stopped. 2 1/2 months later the patient died.

This patient had worked with sheep and human dura mater from 1968 to 1972.He handled about 150 specimens of ovine origin and at least a dozen humanpreparations for research. Handling involved opening skulls with a band saw,removing dura, and testing them either fresh (usually), preserved, orlyophilised for mechanical qualities. These specimens were sent to a companythat has sold dura mater preparations by which CJD was transmitted in sixinstances. No information was available from the company about a possibleconnection with this patient's disease and the earlier cases of transmittedCJD. Brain biopsy was consistent with diagnosis of CJD. Cerebrospinal fluidobtained in July showed neuron-specific enolase (NSE) at 82.0 ng/mL,compared with 16.7 ng/mL in serum of other cases (6). Proton magneticresonance spectroscopy of parieto-occipital and temporal grey matter,parietal white matter, and thalamus revealed a 20-30% reduction ofN-acetylaspartate, as described (7). DNA was genotyped with allele-specificoligonucleotides (8) and was homozygous for methionine at the polymorphiccodon 129. Subsequent direct DNA sequencing for the PrP gene open-readingframe demonstrated normal sequence on both alleles, excluding known or novelpathogenic PrP mutations.

It is tempting to speculate that prions were transmitted to this patientfrom sheep or human dura mater through small lacerations of his skin, butthe patient and his wife did not remember any significant injury during hisfour years of working with these samples. It cannot be excluded that thiswas a case of sporadic CJD although this assumption is unlikely in view ofthe clinical course which was similar to iatrogenic CJD transmitted byperipheral inoculation, such as with human pituitary growth hormone orgonadotropin or to kuru (1). Iatrogenic cases resulting from intracerebralinoculation with the transmissible agent, for instance following dura matergrafts (2-5), present with a dementing picture, as is usual in sporadic CJD,rather than with ataxia as in this case.